The purpose of this proposal is two-fold: (1) to provide protected time and support to Dr. Klerman while she mentors undergraduate, graduate and medical students, post-doctoral fellows and junior faculty towards careers in patient-oriented research (POR) and augments her capabilities in POR; and (2) to conduct POR related to the effects of chronic sleep restriction on performance and sleep. Dr. Klerman is actively involved in both patient-oriented experimental work and mathematical analyses and modeling that will enable translation of research results into real-world applications. Millions of Americans routinely sleep less than six hours per night, an amount shown to be insufficient for maintaining healthy physiologic function, with documented abnormalities in metabolism, immune function, hormones, mood and performance/alertness. Chronic sleep deficiency predisposes an individual to attentional lapses, errors and accidents. The effect of sleep deficiency on performance is pronounced during the biological (circadian) night, particularly when circadian rhythms are not synchronized to the sleep-wake schedule, as may occur in the 15 percent of Americans who are involved in shift work. We recently demonstrated that sleep restriction affects at least two different regulatory processes in the brain that act on different time scales to affect performance. A short-term process builds over hours and can be rapidly recovered within one long sleep episode. A long-term process builds over days-to-weeks of restricted sleep and has a longer time course of recovery. However, we remain in the dark as to how the finite durations of recent sleep and wake episodes and the overall sleep:wake ratio affect the short-term and long-term consequences of sleep deficiency. This is key information for determining appropriate counter-measures and public health education. The experimental work includes 20-hr days in which the wake episode last only 15.33 hrs but the sleep episode lasts 4.67 hrs (i.e., 1:3.3 sleep:wake) with sleep and wake at all (not just habitual) circadian phases. This design, combined with a meta-analysis of data from other non-24-hr day studies with sleep restriction, enables quantification of the importance of sleep and wake episode duration and circadian timing in performance decrements. The results of the proposed work will allow us to determine the dynamics of the short- and long-term consequences of chronic sleep restriction and how they combine with circadian timing to determine performance at any given time. It is important to understand how sleep restriction and circadian timing interact to determine performance so that (i) work shift regulations can be developed to minimize the chances for fatigue-related industrial accidents and motor vehicle crashes and (ii) individuals can responsibly plan their sleep. The mentoring work will address a critical shortage documented in a NHLBI-sponsored report of researchers in sleep and circadian rhythms. The activities outlined in this proposal have implications for science, for public health, and operational (work) situations.